Defence substances of the gut lining: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Lysozyme, beta-defensin (hBD-2): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Lysozyme and beta-defensin 2 (hBD-2) are the body’s own defence substances, made by cells of the gut lining and by immune cells. Lysozyme splits the bacterial cell wall, hBD-2 makes the envelope of bacteria and yeasts permeable; both gather in the mucus layer.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Paneth cells → Lysozyme Lysozyme is a small enzyme found in tears, saliva, breast milk and intestinal secretions. In the gut it comes mainly from Paneth cells; it can be measured in the stool. Source 2, 1↓ depletes Lysozyme attacks the bacterial cell wall, especially the thick, exposed wall of Gram-positive species. Independently of this, as a strongly positively charged protein it can disrupt bacterial envelopes. observed in studies Source 2
   ⚖ When the balance tips

   too much — If there is plenty of lysozyme, more bacterial walls are split, and more fragments arise that immune cells sense as a signal.

   too little — If there is little lysozyme, more bacterial walls stay intact, and Gram-positive bacteria get through the mucus layer more easily.

   observed in studies · Source 2

2. Phagocytes → Lysozyme Lysozyme is a small enzyme found in tears, saliva, breast milk and intestinal secretions. In the gut it comes mainly from Paneth cells; it can be measured in the stool. Source 2, 1↓ depletes Lysozyme attacks the bacterial cell wall, especially the thick, exposed wall of Gram-positive species. Independently of this, as a strongly positively charged protein it can disrupt bacterial envelopes. observed in studies Source 2
   ⚖ When the balance tips

   too much — If there is plenty of lysozyme, more bacterial walls are split, and more fragments arise that immune cells sense as a signal.

   too little — If there is little lysozyme, more bacterial walls stay intact, and Gram-positive bacteria get through the mucus layer more easily.

   observed in studies · Source 2

3. Lysozyme → Cell wall split The bacterial cell wall is made of peptidoglycan, a mesh of sugar chains. Lysozyme splits the bond between N-acetylmuramic acid and N-acetylglucosamine within it. Source 2↓ depletes Once the mesh is cut in many places, the cell wall can no longer withstand the internal pressure of the bacterium, and the cell bursts. established physiology Source 2
   ⚖ When the balance tips

   too much — If a lot of peptidoglycan is split, more bacteria dissolve, and their contents, including further bacterial components, are released.

   too little — Some bacteria modify their cell wall chemically, for example with extra acetyl groups; lysozyme then splits it less well, and the wall stays stable.

   observed in studies · Source 2

4. Cell wall split → Fragments Breaking down the cell wall produces small fragments such as muramyl dipeptide. Immune cells and gut cells recognise them through the sensor NOD2 inside the cell. Source 2, 7↕ both, depending on amount The fragments act as a signal: via NOD2, cells switch on defence genes, including the one for hBD-2. Depending on the setting, lysozyme products can amplify or dampen inflammatory signals. observed in studies Source 2, 7
   ⚖ When the balance tips

   too much — If many fragments arise, NOD2 is stimulated more strongly, and cells make more signalling molecules and defence substances.

   too little — If few fragments arise or NOD2 does not work, this signal stays weak; in cell experiments less hBD-2 is then made.

   observed in studies · Source 7, 2

5. Gut cells → Microbes sensed Components of bacteria and fungi bind to sensors of the gut cell such as Toll-like receptors and NOD2. The signalling molecule IL-1 from immune cells also reports irritation. Source 4, 7↑ supplies Sensing translates contact with microbes into a signal inside the cell. Only then does the gut cell start making hBD-2; shown in cell experiments. observed in studies Source 4, 7
   ⚖ When the balance tips

   too much — If many bacterial components meet the sensors, for example when bacteria multiply at the gut wall, the signal becomes stronger and lasts longer.

   too little — If hardly any stimulus meets the sensors, or NOD2 is altered, the signal fails to appear; in cell experiments hBD-2 production then stays low.

   observed in studies · Source 4, 7

6. Microbes sensed → NF-κB The signals from the sensors converge inside the cell and activate the switch NF-κB. It moves into the nucleus and switches on the gene for hBD-2 there. Source 4, 7↑ supplies Besides hBD-2, NF-κB switches on further defence genes, including signalling molecules that summon immune cells. The switch thus bundles different signals into one common response. observed in studies Source 4, 7
   ⚖ When the balance tips

   too much — If NF-κB stays active for long, the cell keeps making hBD-2 and defence signalling molecules.

   too little — If NF-κB is blocked, hBD-2 production in response to a stimulus largely fails to occur in cell experiments.

   observed in studies · Source 4

7. NF-κB → hBD-2 · Vitamin D hBD-2 is a small, positively charged protein with three sulphur bridges. Gut cells release it into the mucus layer; it passes with the gut contents into the stool and can be measured there. Source 3, 4↓ depletes hBD-2 acts against many Gram-negative bacteria and against yeasts such as Candida. In salty surroundings its effect is markedly weaker in laboratory experiments. observed in studies Source 3
   ⚖ When the balance tips

   too much — If a lot of hBD-2 is made, it gathers in the mucus layer and keeps microbes at a distance; at the same time it attracts more immune cells.

   too little — If little hBD-2 is made, the mucus layer contains less of this defence substance, and bacteria reach the gut wall more easily.

   observed in studies · Source 3, 6

   Field of research — hBD-2 production is being studied in inflammatory conditions of the large intestine. Source 9, 8

8. hBD-2 → Envelope perforated With its positive charge, hBD-2 attaches to the negatively charged envelope of bacteria and fungi. It inserts into the membrane and makes it permeable. Source 3↓ depletes Once the membrane becomes permeable, the microbe loses ions and cannot maintain its energy supply; it dies. This has been shown mainly in laboratory experiments. observed in studies Source 3
   ⚖ When the balance tips

   too much — If a lot of hBD-2 acts, more membranes become permeable; the body’s own cells are hardly affected, because their envelope is charged and built differently.

   too little — If little hBD-2 acts, more membranes stay intact; some bacteria also change the charge of their envelope and so evade binding.

   observed in studies · Source 3

9. hBD-2 → Immune cells attracted hBD-2 binds to the receptor CCR6 on immature dendritic cells and memory T cells. These cells follow the signal into the gut lining. Source 5↑ supplies In this way hBD-2 links immediate defence with adaptive defence: the dendritic cells it attracts pick up foreign components and present them to T cells. observed in studies Source 5
   ⚖ When the balance tips

   too much — If there is plenty of hBD-2, more CCR6-bearing cells are drawn into the gut lining, and the defence response there becomes broader.

   too little — If there is little hBD-2, this attracting signal stays weak, and CCR6-bearing cells follow mainly other signalling molecules.

   observed in studies · Source 5

Further stations

• Paneth cells — at the base of the crypts Paneth cells sit at the base of the crypts of the small intestine. Their granules store defence substances such as lysozyme and alpha-defensins, which they release into the gut contents. Source 1↑ supplies Paneth cells release their granules when they sense bacterial components or nerve signals. In this way they keep the space around the crypt stem cells low in microbes. established physiology Source 1
  ⚖ When the balance tips

  too much — If Paneth cells release a lot, lysozyme and defensins gather in the mucus layer, and fewer bacteria reach the surface of the gut cells.

  too little — If Paneth cells release little, for example because their granules are empty, bacteria move closer to the gut wall; in animal models the make-up of the gut flora then changes.

  observed in studies · Source 1, 6

  Field of research — The function of Paneth cells and their defence substances is being studied in inflammatory bowel conditions. Source 9

• Phagocytes — macrophages, neutrophils Macrophages and neutrophil granulocytes also carry lysozyme. When they migrate into the gut lining they release it there and so add to the amount in the gut. Source 2↑ supplies Inside phagocytes, lysozyme breaks down the cell wall of engulfed bacteria. When many phagocytes are drawn into the gut lining, they bring extra lysozyme with them. established physiology Source 2
  ⚖ When the balance tips

  too much — If many phagocytes gather in the gut lining, the amount of lysozyme there and in the gut contents rises above what Paneth cells release alone.

  too little — If few phagocytes enter the gut lining, the lysozyme in the gut comes mainly from Paneth cells.

  established physiology · Source 2

• Gut cells — of the colonic lining The cells of the colonic lining separate the body from the gut contents. Besides mucus they make defensins: hBD-1 all the time, hBD-2 only in response to a signal. Source 4↑ supplies Gut cells carry sensors for bacteria, fungi and signalling molecules. When a signal arrives, they make extra defence substances and release them into the mucus layer. established physiology Source 4, 6
  ⚖ When the balance tips

  too much — If gut cells are irritated for a long time, they keep making more hBD-2, and it builds up in the mucus layer.

  too little — If hardly any signal reaches the gut cells, only the constant baseline production of hBD-1 remains, and little hBD-2 is found.

  established physiology · Source 4

Cofactors in this pathway

• Vitamin D — Via its receptor, additionally switches on the genes for NOD2 and hBD-2; shown in cell experiments Source 8In the ORY catalogue as a laboratory value: Vitamin D
• Zinc — Stored in Paneth cell granules and released with them; shown in the rat Source 10In the ORY catalogue as a laboratory value: Zink
• Calcium — Present in Paneth cell granules; its rise inside the cell triggers granule release; shown in the mouse Source 10, 11In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Cysteine — Building block of defensins: six cysteines form the three sulphur bridges that hold the protein in shape Source 3

Sources

1. Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011 · PubMed 21423246
2. Ragland SA, Criss AK. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. PLoS Pathog 2017 · PubMed 28934357
3. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003 · PubMed 12949495
4. O'Neil DA, Porter EM, Elewaut D et al. Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 1999 · PubMed 10586069
5. Yang D, Chertov O, Bykovskaia SN et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999 · PubMed 10521347
6. Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol 2016 · PubMed 27498766
7. Voss E, Wehkamp J, Wehkamp K et al. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem 2006 · PubMed 16319062
8. Wang TT, Dabbas B, Laperriere D et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem 2010 · PubMed 19948723
9. Ramasundara M, Leach ST, Lemberg DA et al. Defensins and inflammation: the role of defensins in inflammatory bowel disease. J Gastroenterol Hepatol 2009 · PubMed 19215333
10. Dinsdale D. Ultrastructural localization of zinc and calcium within the granules of rat Paneth cells. J Histochem Cytochem 1984 · PubMed 6693753
11. Ayabe T, Wulff H, Darmoul D et al. Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel. J Biol Chem 2002 · PubMed 11724775

Related pathways

• Lipopolysaccharides — nf-κb
• Bacterial enteric organisms — Vitamin D, Zink
• Borrelia — Vitamin D, Zink
• Clostridioides difficile — Vitamin D, Zink
• Calprotectin — Zink, Calcium (intrazellulär)

As of 2026-10-05. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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